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Smoking is a well-established risk factor for cancer, and cancer patients have a high risk of venous thromboembolism (VTE). Conflicting results have been reported on the association between smoking and risk of VTE, and the effect of smoking on VTE-risk in subjects with cancer is scarcely studied. We aimed to investigate the association between smoking and VTE in subjects with and without cancer in a large population-based cohort. The Scandinavian Thrombosis and Cancer (STAC) cohort included 144,952 participants followed from 1993–1997 to 2008–2012. Information on smoking habits was derived from self-administered questionnaires. Active cancer was defined as the first two years following the date of cancer diagnosis. Former smokers (n = 35,890) and those with missing information on smoking status (n = 3680) at baseline were excluded. During a mean follow up of 11 years, 10,181 participants were diagnosed with cancer, and 1611 developed incident VTE, of which 214 were cancer-related. Smoking was associated with a 50% increased risk of VTE (HR 1.49, 95% CI 1.12–1.98) in cancer patients, whereas no association was found in cancer-free subjects (HR 1.07, 95% CI 0.96–1.20). In cancer patients, the risk of VTE among smokers remained unchanged after adjustment for cancer site and metastasis. Stratified analyses showed that smoking was a risk factor for VTE among those with smoking-related and advanced cancers. In conclusion, smoking was associated with increased VTE risk in subjects with active cancer, but not in those without cancer. Our findings imply a biological interaction between cancer and smoking on the risk of VTE.

Methods VTE identification and validation All first lifetime events of VTE occurring among the participants in this period were identified using the hospital discharge diagnosis registry, the autopsy registry and the radiology procedure registry from University Hospital of North Norway (UNN), which is the sole provider of diagnostic radiology and treatment of VTE in the Tromsø area. Trained personnel adjudicated and recorded each VTE by extensive medical records review. The adjudication criteria for VTE were presence of signs and symptoms of PE or DVT combined with objective confirmation by radiological procedures, which resulted in treatment initiation (unless contraindications were specified). A VTE-event was classified as either a DVT or a PE. When a PE and DVT occurred concurrently, the event was classified as a PE. The identification and adjudication process of VTEs has been previously described in detail 1 .

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Background Although venous thromboembolism (VTE) is associated with a high recurrence rate, the absolute recurrence rates for cancer-related VTE, particularly occult cancer, are not well known. Objectives To investigate the risk of VTE recurrence in patients with occult and overt cancer-related VTE. Methods Incident VTE events among participants of the first to sixth Tromsø surveys occurring in the period 1994-2012 were included. Occult cancer was defined as cancer diagnosed within a year following a VTE, and overt cancer was defined as cancer diagnosed within the 2 years before a VTE. Results Among 733 patients with incident VTE, 110 had overt cancer and 40 had occult cancer. There were 95 recurrent VTE events during a median of 3.2 years of follow-up. The 1-year cumulative incidence of VTE recurrence was 38.6% in subjects with occult cancer, 15.5% in subjects with overt cancer, and 3.8% in non-cancer subjects. The 1-year risk of recurrence was 12-fold (hazard ratio [HR] 12.4, 95% confidence interval [CI] 5.9-26.3) higher in subjects with occult cancer and four-fold (HR 4.3, 95% CI 2.0-9.2) higher in subjects with overt cancer than in non-cancer subjects. The occult cancers associated with VTE recurrence were typically located at prothrombotic sites (i.e. lung and gastrointestinal) and presented at advanced stages. The majority (69%) of recurrences in subjects with occult cancer occurred before or shortly after cancer diagnosis, and were therefore not treatment-related. Conclusion Our findings suggest that the increased risk of recurrence in patients with occult cancer is mainly attributable to the advanced cancers in these patients.